Transcript hiv_and_menopausex

NORTHWEST AIDS EDUCATION AND TRAINING CENTER
HIV and Menopause
Ruanne Barnabas, MBChB, DPhil
Assistant Professor
Departments of Global Health, Medicine and Epidemiology
Date: 9/3/15
This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice
related to any specific patient.
Consequences of aging
as a woman with HIV
Women living with HIV face
all the challenges that the
general population faces
when growing older PLUS:
The consequences of
living longer with HIV
The consequences of
longer exposure to HIV
treatment regimens
Figure adapted from Margaret Johnson
Conditions with
increased incidence
in women living with
HIV:
• Hormonal changes
• Cardiovascular events
• Non-AIDS-defining
infections
• Renal disease
• Non-AIDS-defining
cancers/malignancy
• Muscular and skeletal
changes
• Non-AIDS-dementias,
neurocognitive changes,
mood and CNS disorders
Menopause
• ≥12 consecutive months - amenorrhea (not surgery or
another obvious cause)
• Age at which natural menopause - marker of aging
• Later age at menopause associated with:
- Longer overall survival and greater life expectancy
- Reduced all-cause mortality
- Reduced risk of CV disease, stroke, angina after MI, atherosclerosis
- Preserved bone density and reduced risk of osteoporosis and fracture
- Increased risk of breast, endometrial, and ovarian cancers
Santoro N, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 417–423
Menopause among HIV+ women
Women living with HIV were 73% more likely to experience early onset
of menopause compared with HIV-uninfected women (P=0.024)
Figure adapted from Margaret Johnson
Schoenbaum et al (2005) Clin Infect Dis
Potential contributors to
early onset of menopause in women with HIV
Figure adapted from Margaret Johnson
Immunosuppression
Lower CD4+ count has
been associated with
early menopause
onset
Smoking
Socioeconomic status
Menopause can occur
up to 1–2 years earlier
in smokers, compared
with non-smokers
Markers of low
socioeconomic status
(e.g. lower level of
education,
unemployment and
poverty) have been
associated with early
menopause onset
Inconsistent factors: Race, ethnicity, BMI or body composition, physical activity, diet
Thompson SC et al. AIDS Care 1996;8(1):5-14; Willett W et al. Am J Epidemiol
1983;117:651-658; Cooper GS et al. Epidemiology 1999;10:771-773; Luoto R et al.
Am J Epidemiol 1994;139(1):64-76;
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http://www.cdc.gov/hiv/topics/women/resources/factsheets/pdf/women.pdf
Menopause: Associated changes in health risks
• The menopause - marked by the ending of
menstruation and ovulation
- Falling levels of estrogen
• Onset of the menopause is associated with an
increased risk of:
- Cardiovascular disease (CVD)
- Diabetes
- Osteopenia / osteoporosis
• Early onset menopause (before 46 years):
- Increases the risk of these diseases
- May be linked to increased mortality
Santoro N et al. Maturitas 2009;64:160-164; Carr MC. J Clin Endocrinol Metab 2003;88:2404-2411;
Isaia GC et al. Exp Gerontol 1990;25(3-4):303-307; Kritz-Silverstein
D et al. Am J Public Health
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1993;83:983-988; Lisabeth LD et al. Stroke 2009;40(4):1044-1049
Evaluation of Reproductive Aging and
Predictors of Ovarian Function
• Follicle Stimulating Hormone (FSH)
- Sustained rise in late menopausal transition, and precipitous around the
final menstrual period
- Early follicular phase between cycle days 2 and 5 (more sensitive)
• Estradiol (E2)
- Early follicular levels are the last biomarker of the transition to change
with rapid decline 2 years prior to menopause
• Inhibin B
- Early predictor of menopausal transition
• Anti-Mullerian Hormone(AMH)/ Mullerian Inhibitin Substance (MIS)
- Concentrations decline through reproductive life
- Earliest and most effective way to measure a woman’s progress toward
menopause
• No difference between HIV+ and HIV-negative women
Santoro N; Obstet Gynecol Clin North Am. 2011 Sep; 38(3): 425-440
Estrogen has significant cardiovascular effects,
which include:
A.
B.
C.
D.
Vasodilatation
Prevention of smooth muscle cell proliferation
Inhibition of LDL deposition in the vascular wall
Inhibition of platelet aggregation and stress-induced
endothelial injury
E. All of the above
Menopause Symptoms
• Hot flashes are associated with endothelial dysfunction
– Decreased flow-mediated dilation
– Higher levels of aortic calcification and intima media thickness
of the common carotid artery
• Vaginal dryness
• Sleep disturbances
• Mood disorders
• Decrease QOL
Chae CU, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 477-488
Recommendations for evaluation of bone disease in HIV
A. Screening for osteoporosis all men >50 with Bone
densitometry (DEXA Scan).
B. Screening with DEXA scan all HIV infected postmenopausal
women.
C. Screening with DEXA all HIV infected who have a history of
fragility fracture.
D. Screening with DEXA all receiving chronic glucocorticoid
treatment or at high risk of falls
E. All of the above
Brown, T and colleagues, Bone disease in HIV, CID, 2015
Bone and Menopause
Bone loss accelerates substantially in late peri-menopause and the initial
postmenopausal years. Body weight is a major determinant.
Finkelstein J, et.al; J Clin Endocrinol Metab. 2008 March; 93(3): 861–868
Managing the menopause in women with HIV
• Strategies to offset effects associated with menopause
include:
- Healthy lifestyle choices
- Smoking cessation
- Adherence to effective ART
- HRT – limited data
- Anti-inflammatories - statins
- Symptom management
- Mood/mental health
- Alternative therapies
Kanapathipillai, Menopause, 2013
Algorithm for management of menopause
Kanapathipillai, Menopause, 2013
Management of menopausal symptoms (1)
• Exclude other causes:
- Non HIV related: depression, thyroid, drug side effects,
- HIV related: OI, malignancy including lymphoma
• Lifestyle choices: Smoking cessation and ART adherence
• Alternatives for hot flushes among HIV+ women include:
- Selective serotonin reuptake inhibitor (SSRI) – paroxetine
(inconsistent effect and can inhibit cytochrome P450)
- Serotonin-norepinephrine reuptake inhibitor (SNRI) – venlafaxine
- Gabapentin (consistent effect and no interactions with ART)
- Clonidine
Chae CU, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 477-488
Drug Interactions by ART class
McPheeters, C, JNP, 2013
Management of menopausal symptoms (2)
• Complementary therapies, including omega-3 fatty acids,
and soy-derived isoflaones, decrease symptoms
• Black cohosh (Cimicifuga racemosa) – serious liver
reactions reported
• Topical oestrogen creams or lubricants - Local
administration of oestrogen is not associated with the same
risks as systemic HRT
• Acupuncture
• Yoga
Chae CU, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 477-488
Treatment options for HIV+ women
McPheeters, C, JNP, 2013
Hormone replacement therapy
in women living with HIV
• HRT – SOC until associated with breast ca., stroke, CAD and PE
• Lowest effective dose and shortest possible time – symptoms recur in
50%
• HRT – no guidance for use among HIV+ women
• Risks may outweigh the benefits if they:
- Smoke
- Are overweight
- Have had blood clots, breast cancer, diabetes, high cholesterol levels,
liver problems, or a family history of heart disease
• Estrogen and/or progesterone have interactions with ART (estrogen
interacts with PIs and NNRTIs; NRTIs, integrase inhibitors and entry
inhibitors have no known significant interactions)
Kanapathipillai, Menopause, 2013
Discussion
• Uncomplicated HIV+ woman, treatment options for HIV
uninfected women may be worthwhile
• Check drug interactions
• Need for research to address this gap in evidence for
clinical practice
• Given increasing life-expectancy of HIV+ women, this is a
priority for research